Beneficial effects of ethyl pyruvate in a mouse model of spinal cord injury.
The aim of the present study was to evaluate in a mouse model of spinal cord injury (SCI) the effect of the treatment with ethyl pyruvate (EP). Spinal cord injury was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy in mice. Treatment with EP (75, 25, or 8.5 mg/kg) 1 and 6 h after the SCI significantly decreased (a) the degree of spinal cord inflammation and tissue injury (histological score), (b) neutrophil infiltration (myeloperoxidase activity), (c) nitrotyrosine formation and iNOS expression, (d) proinflammatory cytokines expression, (e) nuclear factor kappaB activation, (f) extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase phosphorylation, and (g) apoptosis (TUNEL staining, Fas ligand, Bax, and Bcl-2 expression). Moreover, EP (75, 25, or 8.5 mg/kg) significantly ameliorated in a dose-dependent manner the loss of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that EP treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.
Genovese
Tiziana
T
IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.
Esposito
Emanuela
E
Mazzon
Emanuela
E
Di Paola
Rosanna
R
Meli
Rosaria
R
Caminiti
Rocco
R
Bramanti
Placido
P
Fink
Mitchell P
MP
Cuzzocrea
Salvatore
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D011773:Pyruvates / Q000493:pharmacokinetics*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
C494827:Bax protein, mouse; D053222:Fas Ligand Protein; D011773:Pyruvates; D051028:bcl-2-Associated X Protein; C046522:ethyl pyruvate; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3